---
res:
  bibo_abstract:
  - "Cell migration is a crucial process in animal development and maintenance. It
    is incredibly\r\nheterogeneous, with different cell types utilizing fundamentally
    distinct migration strategies.\r\nThe strategies also depend on the cellular microenvironment,
    where cells can switch between\r\nmigration modes as they encounter new environmental
    cues. In this thesis, we investigated\r\nhow dendritic cells adapt their migration
    strategy when encountering geometrically,\r\nmechanically and chemically distinct
    environments.\r\nWhen dendritic cells are embedded in a homogeneous fibrous network,
    they migrate in a fast\r\nand directional amoeboid manner. In this migration strategy,
    extracellular proteolysis and\r\nintegrin-mediated adhesions are dispensable.
    Instead, the cells use topography of the\r\nenvironment to propel their cell body
    forward. To migrate efficiently in the maze of different\r\npore sizes, they position
    the nucleus ahead of the microtubule organizing center (MTOC) and\r\nuse it to
    gauge the pores to identify the path of least resistance. Our aim was to identify\r\nwhether
    dendritic cells adapt their migration strategy when encountering asymmetrical\r\ntransitions
    into much denser environments with limited choice of large pores. In such invasive\r\ntransitions
    it is unclear if the cells can cross tight pores without the use of adhesions
    and\r\nextracellular proteolysis and whether they maintain the nucleus in the
    cell front.\r\nUsing various cell migration assays such as fibrous 3D collagen
    gels, geometrically defined\r\nmicrochannels with constrictions and simplistic
    under agarose migration assay, we provide\r\na comprehensive characterization
    of invasive migration of dendritic cells. We show that\r\nduring invasion the
    cells stall and stretch, reflecting the difficulty to translocate the bulky cell\r\nbody
    into the dense environment. In collagen gels, we show that dendritic cells can
    invade\r\nwithout proteolysis and adhesions. Instead, they utilize contractility,
    which can lead to largescale collagen compressions. During invasion, the nucleus
    stalls at tight constrictions, leading\r\nto a transient organelle reorientation.
    To resolve the stalling, upregulated rear contractility is\r\nrequired. This contractile
    force is simultaneously necessary for reverting the nucleus back to\r\nthe cell
    front after invasion and maintaining this positioning during permissive migration.\r\nA
    functional role of the reorientation was uncovered in the first collaboration
    project.\r\nA prominent central actin pool was identified around the MTOC, especially
    pronounced in\r\ndense and compressive environments. The actin pool was shown
    to generate pushing forces\r\nto dilate the space for cell translocation. These
    forces are only necessary in non-permissive\r\nenvironments, where the nucleus
    reorients to the cell rear, allowing the actin pool to\r\ngenerate space. In permissive
    environments where space generation is dispensable, the\r\nMTOC is located behind
    the nucleus and the actin cloud has reduced intensity, allowing more\r\nactin
    to be incorporated into the lamellipodium, speeding up migration.\r\nIn the second
    collaboration project, we investigated the effects of distinct chemical\r\nenvironments
    on dendritic cell migration. The strikingly persistent migration of these cells\r\nwas
    explained by their ability to modulate and even self-generate chemokine gradients.
    This\r\nallows the cells to migrate faster and more persistent in uniform chemokine
    fields compared\r\nto imposed chemokine gradients. The chemokine receptor CCR7
    was identified as a crucial\r\nplayer in this process, both sensing the signal
    and internalizing the chemokine to create a sink.@eng"
  bibo_authorlist:
  - foaf_Person:
      foaf_givenName: Nikola
      foaf_name: Canigova, Nikola
      foaf_surname: Canigova
      foaf_workInfoHomepage: http://www.librecat.org/personId=3795523E-F248-11E8-B48F-1D18A9856A87
    orcid: 0000-0002-8518-5926
  bibo_doi: 10.15479/AT-ISTA-19745
  dct_date: 2025^xs_gYear
  dct_isPartOf:
  - http://id.crossref.org/issn/2663-337X
  - http://id.crossref.org/issn/978-3-99078-058-9
  dct_language: eng
  dct_publisher: Institute of Science and Technology Austria@
  dct_title: Adaptive strategies of dendritic cell migration in response to environmental
    cues@
...